Many studies suggest that hypertensive humans and animal models of hypertension exhibit increased peripheral sympathetic nervous system activity (SNA). Knowledge of the events that lead to elevated SNA and its significance in the genesis and maintenance of elevated blood pressure is rudimentary. Our longrange goal is to understand how blood pressure alters the efficiency of autonomic transmission and how neuroplastic behavior can be modulated for preventive and therapeutic purposes. The objective of this application is to understand the mechanisms by which high blood pressure produces profound changes in the physiology of autonomic synaptic transmission. The general approach is to 1) monitor the activity-dependent and activity-independent changes in neuroplasticity of the sympathetic ganglia isolated from hypertensive rat; 2) monitor the excitability of postganglionic neuron of acutely isolated ganglion cells and their responsiveness during sustained high blood pressure. In animal models of hypertension, our preliminary data show dramatic changes in the electrophysiological behavior of sympathetic ganglion neurons ranging from alterations in the pattern of action potential activity recorded in postganglionic neurons to an enhanced efficacy of synaptic transmission. The central hypotheses are that i) hypertension induces modulation of synaptic efficacy in sympathetic ganglia, and it) Angiotensin II (AnglI), either by long term actions at the ganglion or by increased activation of sympathetic nervous system outflow from the central nervous system, contributes to the alterations in ganglionic function. The rationale for the proposed research is that, once knowledge of the mechanisms that are responsible for alteration of synaptic plasticity in hypertension has been obtained, it will lead to new strategies that can be used to prevent and/or treat hypertension, thereby reducing the morbidity and mortality associated with high blood pressure. The central hypotheses will be tested and the objective of the application will be accomplished by three specific aims. The proposed work is innovative because it capitalizes on the autonomic control of hypertension. It is our expectation that the resultant approach will lead to a better perception of how autonomic ganglia function to regulate blood pressure or vice versa. This proposal uses electrophysiological techniques, receptor autoradiography techniques and neurotransmitter pharmacology in concert with genetic strains of hypertensive animals to learn how genesis and maintenance of high blood pressure alter the function of peripheral neural elements in autonomic ganglia. Such outcomes will be significant because it is expected that the new knowledge will suggest novel targets for preventive and therapeutic interventions.